Little is known of Hopkins before 1644, but apparently he had been a lawyer, practicing in Essex. In March 1644 he alleged his first discovery of witches—six of them, in Manningtree, who he claimed tried to kill him. He thereupon became a “Witch Finder Generall,” going about Essex, Suffolk, Norfolk, and Huntingdon getting villagers and townspeople to hire him and his two assistants (for a fee) to search out witches, force their confessions, and have them hanged by the authorities. Between 1644 and 1647 the hapless victims (including a few Anglican clergymen) numbered perhaps 230 or more.

Many of his methods of inquisition were not far removed from actual torture. He pricked any skin deformity on the accused that was thought to be an extra pap for suckling imps; such parts, if insensible, were believed to prove that the accused was a witch. Another method was to force the accused to walk about all night, for only when at rest could a witch summon his or her familiars, who would terrify the accusers away. A further test was to fling the accused bound into water, because a witch, having denied his or her baptism, would in turn be repelled by the water so that he or she would float and not sink into it.

It has long been propounded that Hopkins was himself accused of being a witch, subjected to his own test of being bound and thrown into water and hanged after he was found to float. In fact, Hopkins died after an illness, likely tuberculosis.